Folic acid and melatonin ameliorate carbon tetrachloride-induced hepatic injury, oxidative stress and inflammation in rats

Hossam Ebaid,Sultan El-Shehry,Ahmed Rady,Samir Ae Bashandy,Ibrahim M Alhazza

doi:10.1186/1743-7075-10-20

Hossam Ebaid, Sultan El-Shehry + Show 3 more

Open Access

https://doi.org/10.1186/1743-7075-10-20

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Abstract

This study investigated the protective effects of melatonin and folic acid against carbon tetrachloride (CCl4)-induced hepatic injury in rats. Oxidative stress, liver function, liver histopathology and serum lipid levels were evaluated. The levels of protein kinase B (Akt1), interferon gamma (IFN-γ), programmed cell death-receptor (Fas) and Tumor necrosis factor-alpha (TNF-α) mRNA expression were analyzed. CCl4 significantly elevated the levels of lipid peroxidation (MDA), cholesterol, LDL, triglycerides, bilirubin and urea. In addition, CCl4 was found to significantly suppress the activity of both catalase and glutathione (GSH) and decrease the levels of serum total protein and HDL-cholesterol. All of these parameters were restored to their normal levels by treatment with melatonin, folic acid or their combination. An improvement of the general hepatic architecture was observed in rats that were treated with the combination of melatonin and folic acid along with CCl4. Furthermore, the CCl4-induced upregulation of TNF-α and Fas mRNA expression was significantly restored by the three treatments. Melatonin, folic acid or their combination also restored the baseline levels of IFN-γ and Akt1 mRNA expression. The combination of melatonin and folic acid exhibited ability to reduce the markers of liver injury induced by CCl4 and restore the oxidative stability, the level of inflammatory cytokines, the lipid profile and the cell survival Akt1 signals.

Highlights

Carbon tetrachloride (CCl4) is a well-known compound for the production of chemical hepatic injury [1] mediated by metabolites that react with antioxidant enzymes, such as glutathione (GSH), catalase and superoxide dismutase, [2] and increase the level of inflammatory cytokines
Effects of melatonin and folic acid on CCl4-induced oxidative stress The results revealed that CCl4 significantly elevated both the concentration of hydroperoxide and the amount of lipid peroxidation
The concentration of glutathione in animals treated with melatonin, folic acid and their synergic combination was four to six-fold higher (p < 0.05) than the concentration of glutathione measured in the CCl4-treated group

Summary

Introduction

Carbon tetrachloride (CCl4) is a well-known compound for the production of chemical hepatic injury [1] mediated by metabolites that react with antioxidant enzymes, such as glutathione (GSH), catalase and superoxide dismutase, [2] and increase the level of inflammatory cytokines. Antioxidants exhibit a strong protection against CCl4-induced hepatic toxicity [3,4]. Previous studies have shown that melatonin and folic acid are very potent antioxidants that scavenge reactive oxygen species (ROS) [5]. Melatonin has been found to be more effective in the protection against oxidative damage than other antioxidants, including. Folic acid has been reported to have an antioxidant effect against ROS and an alleviating role in hyperhomocysteinemia and its associated endothelial dysfunction [19]. The anti-inflammatory effect of folic acid is manifested by a decrease in the levels of interleukin and C-reactive proteins [20]

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